Essence of this Article

Improvements in the management of patients with acute coronary syndrome (ACS) and the routine use of antiplatelet therapy have resulted in considerable reductions in recurrence rates and mortality. The risk of a recurrent ACS event remains high however, and there is a need for therapies that can address the residual rate of recurrent events. One such approach that warrants investigation is the addition of oral anticoagulation to antiplatelet therapy. Risk stratification schemes can be used to translate patient characteristics into the probability of experiencing a recurrent ACS event. The GRACE risk score is one such tool for assessing the mid-term risk of mortality after an ACS event.

Risk of recurrent events in acute coronary syndrome

Before the introduction of routine antiplatelet therapy, recurrence rates and mortality in patients with ACS were high. However, improvements in patient management (such as earlier initiation of therapy, increased use of PCI) and the routine use of antiplatelet therapy have resulted in considerable reductions in recurrence rates and mortality. From 1961 to 2009 there was an approximately 50% reduction in the number of deaths from coronary heart disease, with even greater benefits seen in elderly patients.

Coronary heart disease events remain significantly more likely to be fatal in patients with a history of MI than in those without, with a 2.5-fold increase reported in an observational study.225 Furthermore, the rate of sudden death in patients who have experienced an MI is four to six times higher than in the general population.218 In view of these statistics, the efficacy of antiplatelet therapy, initially ASA, in reducing the risk of serious vascular events in patients at increased risk, including those with prior or acute events, is of particular importance and is now well established.226-228 The addition of a second antiplatelet drug (e.g. clopidogrel) to ASA has been shown to provide additional benefit.229, 230 The routine use of ASA and dual antiplatelet therapy with ASA and clopidogrel has significantly reduced the impact of ACS on patients’ lives. More recently, the antiplatelet agents prasugrel and ticagrelor have demonstrated further improvements in patient outcomes after ACS.231, 232

Collectively these improvements in therapy have led to reductions of almost 50% in early mortality after STEMI or NSTEMI233 over the past decade.

These advances represent major improvements in the treatment of ACS, but the risk of a recurrent ACS event remains high. Recent clinical studies suggest a residual rate of recurrent events of approximately 10% per annum after an initial ACS event,231, 232 with most of these events occurring after discharge from hospital.234
Although the benefits of dual antiplatelet therapy are clear, there is a need for therapies that can address the residual rate of recurrent events. In light of our understanding of the pathogenesis of ACS, one such approach that warrants investigation is the addition of oral anticoagulation to antiplatelet therapy. A number of recent trials have evaluated the potential benefits of such an approach.

The goals of secondary prevention strategies after ACS are twofold:221, 222

Prevention of thrombus formation and recurrence

Management of underlying disorders (e.g. hypertension, diabetes,dyslipidaemia) and other risk factors by medical and other means

Risk stratification schemes can be used to translate patient characteristics into the probability of experiencing a recurrent ACS event.

The Global Registry of Acute Coronary Events (GRACE) risk score is a tool for assessing the mid-term risk of mortality after an ACS event. The GRACE risk score is based on data from the global GRACE registry and is used to predict mortality from hospital discharge to 6 months after an ACS event.235 Another tool based on data from the GRACE registry is used upon admission to estimate the risk of in-hospital mortality.236

Factors included in the GRACE score for prediction of mortality from hospital discharge to 6 months are:235